Chronic treatment of rats with lithium for three weeks decreased the binding of [3H]-spiroperidol to the caudate nucleus as revealed by autoradiographic techniques. Similar treatment also decreased opiate receptors in this structure. The in vitro addition of lithium to tissue homogenates from the striatum, cortex or hippocampus was found to inhibit the binding of [3H]-QNB. However, this was not due to an alteration in muscarinic cholinergic receptors since washing the tissue to remove the lithium reversed the inhibition. Chronic exposure of rats to lithium also did not produce any permanent changes in density of muscarinic binding sites.